This project will investigate the relation between endogenous levels of estrogen in postmenopausal women and the subsequent development of coronary heart disease. Studies suggest ~that estrogen replacement therapy (ERT) lowers the risk of coronary heart disease in postmenopausal women. However, it is not known whether higher endogenous levels of estrogens in the postmenopausal period likewise have a protective effect. The project will utilize an existing resource of frozen blood samples from a cohort of 7058 postmenopausal women enrolled between 1985 and 1991 for a study of endogenous hormones and cancer. The cohort will be followed up to identify incident cases of coronary heart disease. One hundred thirty cases of coronary heart disease (defined as nonfatal myocardial infarction or death from coronary heart disease) are expected to occur by the end of follow-up. A nested case-control study will be conducted in which each case will be matched to two women from the cohort who are the same age as the case, donated blood around the same time, and were alive and free of heart disease as of the date of diagnosis of the case. Frozen serum samples from cases and their matched controls will be analyzed for total estradiol, bioavailable estradiol (the estradiol fraction not bound to sex hormone binding globulin) estrone, total cholesterol, and high- and low-density lipoprotein cholesterol. Conditional logistic regression for matched sets will be employed to determine whether estrogen levels are lower in the cases than their matched controls. The association between estrogen levels and cholesterol fractions will also be investigated.